A highly efficient method to incorporate the nonafluoro- tert-butoxy group into various arenes is developed. This C-O cross-coupling reaction proceeds smoothly in the absence of transition-metal catalyst with good functional group tolerance and scalability. In comparison with the conventional approach, this method avoids the use of nonafluoro- tert-butyl alcohol as the reaction solvent and does not require handling of hazardous diazonium salts. A series of OC(CF3)3-containing analogues of 19F NMR-based probes targeting various biologically relevant analytes are prepared.